Epidermal growth factor (EGF) and transforming growth factor-α (TGF-α) are ligands which interact with the same cell surface receptor, EGF-receptor, and which act as mitogens for a variety of tissues. Groenen et al. (1994) Growth Factors 11:235-257. Based on sequence similarity, mitogenic activity, and the ability to interact with the EGF-receptor, several other EGF family members have been identified including amphiregulin, heparin-binding EGF (HB-EGF), and betacellulin. Carpenter et al. (1990) Handbook Exptl. Pharmacol. 95(1):69-171; Massague et al. (1993) Ann. Rev. Biochem. 62:515-541; Shing et al. (1993) Science 259:1604-1607.
Both EGF and TGF-α have been associated with a variety of processes ranging from wound healing to carcinogenesis. Burgess et al. (1989) Br. Med. Bull. 45:401-424; Massague et al. (1983) J. Biol. Chem. 258:13614-13620; Ozanne et al. (1986) J. Pathol. 149:9-14.
In particular, EGF and TGF-α both induce proliferation of dermal fibroblasts. Buckley-Sturrock et al. (1989) J. Cell. Physiol. 138:70-78; Laato et al. (1987) J. Biochem. 247:385-388; Paulsson et al. (1987) Nature 328:715-717. In addition, EGF exerts proliferative and chemotactic effects on granulation-tissue-derived fibroblasts and induces collagenase and hyaluronic acid synthesis. Laato (1988) Acta. Chir. Scand. Suppl. 546:4-44. EGF has also been reported to stimulate keratinocyte proliferation and migration in vitro, further implicating an important role for EGF in the reepithelialization of wounds. Barrandon et al. (1987) Cell 50:1131-1137; Chernoff (1990) Tissue Cell. 22:123-135.
A number of different cancer cell lines exhibit elevated levels of EGF receptors and TGF-α has been implicated as an autocrine growth factor for many carcinomas. Groenen et al. (1994) Growth Factors 11:235-257. Tumour-derived TGF-α is angiogenic, and it has been predicted that an antagonist of TGF-α may inhibit tumour angiogenesis and/or inhibit the growth of a carcinoma. Groenen et al. (1994) Growth Factors 11:235-257; Okamura et al. (1992) Biochem. Biophys. Res. Comm. 186:1471-1479.